Variant chr20-11919826-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014962.4(BTBD3):c.526G>A(p.Ala176Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

BTBD3
NM_014962.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

Variant links:

Genes affected

BTBD3 (HGNC:15854): (BTB domain containing 3) Enables identical protein binding activity. Predicted to be involved in cerebral cortex development and dendrite morphogenesis. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BTBD3 links:

BTBD3 (HGNC:):

BTBD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30098498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD3	NM_014962.4 linkuse as main transcript	c.526G>A	p.Ala176Thr	missense_variant	3/4	ENST00000378226.7	NP_055777.1	Q9Y2F9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD3	ENST00000378226.7 linkuse as main transcript	c.526G>A	p.Ala176Thr	missense_variant	3/4	1	NM_014962.4	ENSP00000367471.2		Q9Y2F9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251398

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461248

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2022

The c.526G>A (p.A176T) alteration is located in exon 3 (coding exon 3) of the BTBD3 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the alanine (A) at amino acid position 176 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.20

.;.;T;.;.;T;.;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

.;.;.;T;.;D;D;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.30

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.4

.;.;L;.;.;L;.;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.54

N;N;N;N;.;N;.;N;N

REVEL

Benign

0.15

Sift

Benign

0.25

T;T;T;T;.;T;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T

Polyphen

0.17

.;.;B;.;.;B;.;.;.

Vest4

0.41

MutPred

0.56

.;.;Loss of ubiquitination at K179 (P = 0.1815);.;.;Loss of ubiquitination at K179 (P = 0.1815);.;.;.;

MVP

0.90

MPC

0.67

ClinPred

0.065

GERP RS

6.1

Varity_R

0.12

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over